Exposure to benzo(a)pyrene (BP), an ubiquitous carcinogen, may be unusually high for individuals in certain occupations. Formation of BP-DNA adducts due to human exposure is most likely to be at very low levels that are beyond the sensitivity of radioimmunoassay and chromatographic analyses. Thus, ultra-sensitive enzymatic radioimmunoassay (USERIA) and enzyme-linked immunosorbent assay (ELISA) have been employed to detect and quantitate BP-DNA antigenicity in humans at high cancer risk due in part to BP exposure. DNA isolated from white blood cells of asphalt workers (roofers), foundry workers, and DNA from lung tissue, bronchial washing and alveolar macrophages of lung cancer patients, smokers, etc., are being investigated. BP-DNA antigenicity has been detected in several of the high risk individuals. Preliminary data on sera of some of these individuals also suggest presence of anti BP-DNA antibodies. These data suggests the activation of BP to its ultimate carcinogen as well as formation of adducts with DNA occurs in humans.